DSC-MRI in Measuring rCBV for Early Response to Bevacizumab in Patients With Recurrent Glioblastoma

Recurrent Glioblastoma Clinical Trial

Official title:

Change in Relative Cerebral Blood Volume as a Biomarker for Early Response to Bevacizumab in Patients With Recurrent Glioblastoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03115333
• Other study ID #: EAF151
• Secondary ID: NCI-2016-01357EA
• Status: Recruiting
• Phase: N/A
• Start date: July 25, 2017
• Est. completion date: May 7, 2027

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI) works in measuring relative cerebral blood volume (rCBV) for early response to bevacizumab in patients with glioblastoma that has come back. DSC-MRI may help evaluate changes in the blood vessels within the cancer to determine a patient?s response to treatment.

Description:

PRIMARY OBJECTIVES: I. To determine whether binary changes (increase versus [vs.] decrease) in rCBV within enhancing tumor from baseline to 2 weeks after initiation of anti-angiogenic therapy is associated with overall survival (OS). SECONDARY OBJECTIVES: I. To determine whether the baseline pre-treatment rCBV measure alone is associated with OS. II. To determine whether binary changes (increase vs. decrease) in rCBV within enhancing tumor from baseline to 2 weeks after initiation of anti-angiogenic therapy is associated with progression-free survival (PFS). III. To determine whether changes in rCBV as a continuous variable within enhancing tumor from baseline to 2 weeks after initiation of anti-angiogenic therapy is associated with OS or PFS. IV. To determine the association between rCBV and OS when adjusting for the changes in enhancing tumor volume. V. To determine whether baseline cerebral blood flow (CBF) or change in CBF is associated with OS or PFS. OUTLINE: Patients undergo DSC-MRI within 3 days before bevacizumab initiation and at day 15. After completion of study intervention, patients are followed up every 3 months for 1 year and then every 6 months for up to 4 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 146
• Est. completion date: May 7, 2027
• Est. primary completion date: May 7, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically proven intracranial glioblastoma or gliosarcoma at initial surgery
• Patients will be eligible if the original histology was low-grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma is made (high-grade transformation)
• Karnofsky performance status >= 70
• Women must not be pregnant or breast-feeding
• Progression of disease assessed by local site using Revised Assessment in Neuro-Oncology (RANO) criteria, with plan to give whole-dose bevacizumab therapeutically, either as single therapy or in conjunction with other chemotherapeutic regimens; patients getting bevacizumab to support additional radiation therapy or immunotherapy, or primarily for reduction of edema rather than for tumor treatment, are excluded; this must be the patient?s initial recurrence
• Patient must not have been treated previously with immunotherapies (vaccines, checkpoint inhibitors, T-cells)
• Intratumoral hemorrhage (acute, subacute, or chronic) as seen on hemosiderin-sensitive (gradient-echo) MRI may preclude patient inclusion because of anticipated limited evaluation due to magnetic susceptibility artifact on the heavily T2-weighted DSC-MRI images; if the region of enhancing tumor not affected by blooming artifact on the hemosiderin-sensitive images does not meet the 10 x 10 x 10 mm ?measurable enhancement? threshold specified elsewhere, the patient is ineligible
• Progressive enhancement (> 25% increase in contrast enhancing volume compared to nadir) on MRI within 14 days of registration, >= 42 days since completion of radiation/temozolomide therapy, and >= 28 days since surgical resection or cytotoxic chemotherapy; measurable enhancement is defined as two perpendicular in-plane diameters of at least 10 mm and at least 10 mm in the 3rd orthogonal direction
• Patients must be able to tolerate brain MRI scans with dynamic intravenous gadolinium-based contrast agent injections
• Ability to withstand 22 gauge intravenous (IV) placement
• No history of untreatable claustrophobia
• No magnetic resonance (MR) incompatible implants/devices or metallic foreign bodies
• No contraindication to intravenous contrast administration
• Adequate organ function, including adequate renal function defined as estimated glomerular filtration rate (eGFR) >= 40 mL/min/1.73 m^2 as calculated per institution standard of care, and meeting local site requirements for intravenous administration of gadolinium-based MRI contrast agents
• No known allergy-like reaction to gadolinium or moderate or severe allergic reactions to one or more allergens as defined by the American College of Radiology (ACR); patient may be eligible if willing to undergo pre-treatment as defined by the institution's policy and/or ACR guidance
• Weight compatible with limits imposed by the MRI scanner table
• Patient must be scheduled to receive treatment with a standard dose regimen of bevacizumab (bevacizumab infusion on days 1 and 15 of a 28-day treatment cycle); patient can be treated with bevacizumab alone or in combination with other chemotherapies Exclusion Criteria: (see Inclusion Criteria)

Related Conditions & MeSH terms

• Glioblastoma
• Gliosarcoma
• Recurrence
• Recurrent Glioblastoma

Intervention

Diagnostic Test:
• Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging
Undergo DSC-MRI

Locations

Country	Name	City	State
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Maryland Proton Treatment Center	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Boca Raton Regional Hospital	Boca Raton	Florida
United States	Eden Hospital Medical Center	Castro Valley	California
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	University of Cincinnati/Barrett Cancer Center	Cincinnati	Ohio
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Northside Hospital-Forsyth	Cumming	Georgia
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	East Carolina University	Greenville	North Carolina
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Memorial Hermann Texas Medical Center	Houston	Texas
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	IU Health Methodist Hospital	Indianapolis	Indiana
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Baptist Health Lexington	Lexington	Kentucky
United States	Loma Linda University Medical Center	Loma Linda	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Froedtert Menomonee Falls Hospital	Menomonee Falls	Wisconsin
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	VA Palo Alto Health Care System	Palo Alto	California
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	Saint Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Mayo Clinic	Rochester	Minnesota
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	University Hospital	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Moffitt Cancer Center	Tampa	Florida
United States	Moffitt Cancer Center - McKinley Campus	Tampa	Florida
United States	Moffitt Cancer Center-International Plaza	Tampa	Florida
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Froedtert West Bend Hospital/Kraemer Cancer Center	West Bend	Wisconsin
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in rCBV within enhancing tumor	Will determine whether binary changes (increase vs. decrease) in rCBV is associated with OS. Kaplan-Meier survival curves will be generated for both the increased and the decreased rCBV groups. The median survival time of both groups will be estimated and compared with a two-sided log rank test. Univariate Cox proportional hazards model will be used to test the association between changes in rCBV from baseline to 2 weeks and OS or PFS.	Baseline to 2 weeks
Primary	OS	Will determine if binary changes (increase vs. decrease) in rCBV is associated with OS. The median survival time of both groups will be estimated and compared with a two-sided log rank test. Will determine whether changes in rCBV as a continuous variable within enhancing tumor from baseline to 2 weeks after initiation of anti-angiogenic therapy is associated with OS. Univariate Cox proportional hazards model will be used to test the association between changes in rCBV from baseline to 2 weeks and OS. The hazard ratio and its 95% confidence interval (CI) will be presented. Will determine the as	Up to 5 years
Secondary	CBF	Will determine if baseline CBF is associated with OS or PFS. Kaplan-Meier survival curves will be generated for both the increased and the decreased CBF groups, for either OS or PFS. The median survival time/progression free survival time of both groups will be estimated and compared with a two-sided log rank test. Univariate Cox proportional hazards model will be used to test the association between baseline CBF and OS or PFS. The hazard ratio and its 95% CI will be presented.	Baseline
Secondary	Change in CBF	Will determine if changes in CBF is associated with OS or PFS. Kaplan-Meier survival curves will be generated for both the increased and the decreased CBF groups, for either OS or PFS. The median survival time/progression free survival time of both groups will be estimated and compared with a two-sided log rank test. The hazard ratio and its 95% CI will be presented.	Baseline to 2 weeks
Secondary	PFS	Will determine whether binary changes (increase vs. decrease) in rCBV within enhancing tumor from baseline to 2 weeks after initiation of anti-angiogenic therapy is associated with PFS. Will determine whether changes in rCBV as a continuous variable within enhancing tumor from baseline to 2 weeks after initiation of anti-angiogenic therapy is associated with PFS. Univariate Cox proportional hazards model will be used to test the association between changes in rCBV from baseline to 2 weeks and PFS. Kaplan-Meier survival curves will be generated for both the increased and the decreased rCBV grou	Up to 5 years
Secondary	rCBV	Will determine whether the baseline pre-treatment rCBV measure alone is associated with OS. Univariate Cox proportional hazards model will be used to test the association between baseline rCBV and OS. The hazard ratio and its 95% confidence interval will be presented.	Baseline